A new study suggests, however, that starting those patients on triple therapy of metformin, pioglitazone, and the glucagon-like peptide-1 (GLP-1) agonist exenatide, marketed as Byetta by AstraZeneca/Bristol-Myers Squibb, has significant benefits over typical treatment in reducing HbA1c, hypoglycemia, and weight gain.

The study, lead by Muhammad A. Abdul-Ghani, MD, PhD, of the University of Texas Health Science Center at San Antonio, was presented at the American Diabetes Association (ADA) 2013 Scientific Sessions in Chicago.

According to the study background, “step-wise addition of metformin sulfonylurea and basal insulin reduced microvascular complications, but A1c rose progressively to [greater than] 8.5% and [about] 65% of individuals required insulin therapy after 10.5 years.” Researchers sought to determine the efficacy and safety of initiating therapy in new-onset diabetes patients with the triple therapy approach instead of metformin followed by sequential addition of sulfonylurea and basal insulin, a treat-to-fail approach.

The study involved 147 type 2 diabetes patients, diagnosed within the last 6 months, and with an average age of 45, BMI around 36, and A1c about 8.6. Of the study group, 71 were randomized to receive the so-called triple therapy, an initial combination of metformin (1,000-2,000 mg/d) plus pioglitazone (15-45 mg/d) plus exenatide (5-10 mcg BID). At the same time, 76 received conventional therapy, an escalating dose of metformin (1,000-2,000 mg/d) followed by sequential addition of glipizide (5-20 mg/d) and then basal insulin to maintain A1c < 6.5%.

“In subjects receiving triple therapy, A1c decreased from 8.6 to 6.1% at six months and remained stable at 6.1% at 24 months,” according to the authors. “With conventional therapy, A1c declined to 6.1% at six months and then increased to 6.6% at 24 months.”

In addition, more patients in the conventional therapy group failed to achieve the treatment A1c goal of under 6.5% (46% vs. 22% P < 0.0001). The authors also noted that, despite significantly lower A1c, subjects in the triple-therapy group experienced a 13.6-fold lower rate of hypoglycemia compared to patients in the other group. They also had mean weight loss of 1.2 kg versus 3.6 kg weight gain (P = 0.02) in subjects on conventional therapy.